Expression of the vitamin d receptor is increased in the hypertrophic heart.
The liganded vitamin D receptor (VDR) is thought to play an important role in controlling cardiac function. Specifically, this system has been implicated as playing an antihypertrophic role in the heart. Despite this, studies of VDR in the heart have been limited in number and scope. In the present study, we used a combination of real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and transient transfection analysis to document the presence of functional VDR in both the myocytes and fibroblasts of the heart, as well as in the intact ventricular myocardium. We also demonstrated the presence of 1-alpha-hydroxylase and 24-hydroxylase in the heart, 2 enzymes involved in the synthesis and metabolism of 1,25 dihydroxyvitamin D. VDR is shown to interact directly with the human B-type natriuretic peptide gene promoter, a surrogate marker of the transcriptional response to hypertrophy. Of note, induction of myocyte hypertrophy either in vitro or in vivo leads to an increase in VDR mRNA and protein levels. Collectively, these findings suggest that the key components required for a functional 1,25 dihydroxyvitamin D-dependent signaling system are present in the heart and that this putatively antihypertrophic system is amplified in the setting of cardiac hypertrophy.
Chen
Songcang
S
Diabetes Center, University of California at San Francisco, CA 94143-0540, USA.
Glenn
Denis J
DJ
Ni
Wei
W
Grigsby
Christopher L
CL
Olsen
Keith
K
Nishimoto
Minobu
M
Law
Christopher S
CS
Gardner
David G
DG
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008156:Luciferases / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D010714:Phosphatidylethanolamines; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism
D010714:Phosphatidylethanolamines; D018167:Receptors, Calcitriol; D020097:Natriuretic Peptide, Brain; D014807:Vitamin D; C100004:transfectACE; C097949:1,25-dihydroxyvitamin D; D008156:Luciferases